This proposal will seek to determine the characteristics and prognostic relevance of circulating tumor cell measurements in patients with metastatic non-small cell lung carcinoma. The use of circulating tumor cell determinations has already shown to be useful in the care of patients with metastatic breast cancer. The currently available technology is not suitable for use in non-small cell lung cancer due to the heterogeneity of cell markers that are required for circulating tumor cell measurement as presently performed. We will leverage the current investment by the National Institutes of Health for the development of the FAST cytometer as a tool for rare event imaging and apply it to lung cancer. This proposal will test the hypothesis that circulating tumor cell determinations can serve as a useful prognostic marker in non-small cell lung cancer by achieving the following specific aims: 1. To characterize circulating tumor cells in patients with non-small cell lung cancer 2. To prospectively determine the correlation between circulating tumor cell count and survival in metastatic non-small cell lung cancer 3. To correlate the effect of standard lung cancer drug therapy efficacy with circulating tumor cell count. We will use a training set of patients to determine the cell morphology and prevalence of circulating tumor cells in patients with metastatic disease. The morphologic and numeric determinants of circulating tumor cells on patient survival will then be validated in a separate patient cohort. Subsequently, patients will be followed over the history of their disease to establish the effect of drug therapy on these cells.